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    Evidence of CD4(+) T cell-mediated immune pressure on the Hepatitis C virus genome

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    Author
    Lucas, M; Deshpande, P; James, I; Rauch, A; Pfafferott, K; Gaylard, E; Merani, S; Plauzolles, A; Lucas, A; McDonnell, W; ...
    Date
    2018-05-08
    Source Title
    Scientific Reports
    Publisher
    NATURE PUBLISHING GROUP
    University of Melbourne Author/s
    Drummer, Heidi
    Affiliation
    Microbiology and Immunology
    Metadata
    Show full item record
    Document Type
    Journal Article
    Citations
    Lucas, M., Deshpande, P., James, I., Rauch, A., Pfafferott, K., Gaylard, E., Merani, S., Plauzolles, A., Lucas, A., McDonnell, W., Kalams, S., Pilkinton, M., Chastain, C., Barnett, L., Prosser, A., Mallal, S., Fitzmaurice, K., Drummer, H., Ansari, M. A. ,... Gaudieri, S. (2018). Evidence of CD4(+) T cell-mediated immune pressure on the Hepatitis C virus genome. SCIENTIFIC REPORTS, 8 (1), https://doi.org/10.1038/s41598-018-25559-6.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/255147
    DOI
    10.1038/s41598-018-25559-6
    Abstract
    Hepatitis C virus (HCV)-specific T cell responses are critical for immune control of infection. Viral adaptation to these responses, via mutations within regions of the virus targeted by CD8+ T cells, is associated with viral persistence. However, identifying viral adaptation to HCV-specific CD4+ T cell responses has been difficult although key to understanding anti-HCV immunity. In this context, HCV sequence and host genotype from a single source HCV genotype 1B cohort (n = 63) were analyzed to identify viral changes associated with specific human leucocyte antigen (HLA) class II alleles, as these variable host molecules determine the set of viral peptides presented to CD4+ T cells. Eight sites across the HCV genome were associated with HLA class II alleles implicated in infection outcome in this cohort (p ≤ 0.01; Fisher's exact test). We extended this analysis to chronic HCV infection (n = 351) for the common genotypes 1A and 3A. Variation at 38 sites across the HCV genome were associated with specific HLA class II alleles with no overlap between genotypes, suggestive of genotype-specific T cell targets, which has important implications for vaccine design. Here we show evidence of HCV adaptation to HLA class II-restricted CD4+ T cell pressure across the HCV genome in chronic HCV infection without a priori knowledge of CD4+ T cell epitopes.

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